Letter from Otto Bier, Instituto Biologico (Brazil) to Michael Heidelberger
In this letter Otto Bier, one of Heidelberger's former postdoctoral students, illustrated how World War II affected scientific
research, in this case in Brazil. Bier also reported results of his research on complement, a complex system of over twenty
serum proteins that play an essential enzymatic role in host defense mechanisms against invading organisms. Heidelberger
became one of the founders of the study of complement when he showed during the 1940s that it was a group of specific chemical
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1944-09-11 (September 11, 1944)
[Instituto Biologico (Brazil)]
Reproduced with permission of the Instituto Biologico, Avenida Conselheiro Rodrigues Alves
Medical Subject Headings (MeSH):
Complement System Proteins
World War II
Antigens and Antibodies: Heidelberger and The Rise of Quantitative Immunochemistry, 1928-1954
Many thanks for your kind 1etter of April which arrived here only in July. The manuscript on bovine complement sent to you
has apparently been lost on the way, so I am sending you another copy.
It my interest you to know that I have been appointed Director of Butantan Institute - the well known Institute for the preparation
of snake antivenoms. This represents, of course, a great honor to me, but at the same time a misfortune: very little time
for the laboratory and a lot of administrative work to do. Guilty is Prof. Rocha Lima, my former Director at the Biological
Institute, who suggested my name to the government. (I know that now). I could not simply say no to the invitation since there
is a lot of war work to do at Butantan, such as vaccines and antitoxins, liophilization of human blood plasma for the armed
forces, etc. Anyhow, I expect to be released from this "big shot" job soon after the war and go back to my laboratory
at the Biological Institute. I also dream already with the possibility to return to the United States, when, with peace of
mind, I shall be able to work with you on that "No. 1 Jig Saw Puzzle" you talked about in your letter.
By ordinary mail I am sending you the reprint of a paper published in the Rev. Bras. Biol. on the order of fixation of the
complement-components. I should like to draw your attention to a very simple experiment referred in that paper, the interpretation
of which is still obscure to me: If you take sensitised cells, add NH3 - Serum, incubate at 37 degrees and after varying intervals
add 56 degrees - Serum, you will have a result like that:
Simultaneous addition of NH3 and 56 degrees Serum - Complete hemolysis in 3 minutes.
56 degrees - Serum added 10 minutes after the NH3 - Serum - C.H. in 3'.
56 degrees - Serum added 20 minutes after the NH3 - Serum - C.H. in 10'.
56 degrees - Serum added 30 minutes after the NH3 - Serum - C.H. in 40'.
56 degrees - Serum added 60 minutes after the NH3 - Serum - Partial Hemolysis in 60'.
56 degrees - Serum added 120 minutes after the NH3 - Serum - No hemolysis in 60'.
I think that this simple experiment lends further support to the idea that C'4 and C'1 must be fixed simultaneously
for the full development of the hemolytic activity of the complement.
I am now making quantitative determinations on a Ramon type of flocculation with snake (Crotalus) venom and the specific antivenom:
the ratio between antivenom-N and venom-N seems to be very close to 10 (the venom has been
chemically studied by Slotta et al, who isolated and crystallised a protein with a molecular weight of 33.000).
Unfortunately, as I said before, the research work has to be done in the intervals of administrative work, and it takes months
to do a thing that you could have done in a few weeks.
I also hope that you will be released soon from all the war work you must have, although it is interesting too.
With my best greetings to all the friends at the laboratory (Manfred,
Mrs. McPherson, Soo-Hoo, Mary) and my special regards to Mrs. Heidelberger,
also from my wife,